Crown ether analogs from sucrose

Article abstract of DOI:10.1081/CAR-100106931

A convenient synthesis of 1′,2,3,3′4,4′-hexa-O-benzylsucrose (4) from the free disaccharide is presented. Diol 4 and previously obtained 1′-O-benzyloxymethyl-2,3,3′,4,4′-penta-O-benzylsucrose (3) served as precursors for chiral crown ether analogs containing a sucrose backbone. Deprotection of macrocyclic compounds (removal of the benzyl blocks) was possible under hydrogenolysis conditions.

Full text of DOI:10.1081/CAR-100106931

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CROWN ETHER ANALOGS FROM SUCROSE
Mateusz Mach a , Slawomir Jarosz b & Arkadiusz Listkowski a
a Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52,
Warszawa, 01-224, Poland
b Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52,
Warszawa, 01-224, Poland
Version of record first published: 19 Aug 2006.
To cite this article: Mateusz Mach, Slawomir Jarosz & Arkadiusz Listkowski (2001): CROWN ETHER ANALOGS FROM
SUCROSE, Journal of Carbohydrate Chemistry, 20:6, 485-493
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J. CARBOHYDRATE CHEMISTRY, 20(6), 485–493 (2001)
CROWN ETHER ANALOGS FROM SUCROSE
Mateusz Mach, Slawomir Jarosz,* and Arkadiusz Listkowski
Institute of Organic Chemistry, Polish Academy of Sciences,
Kasprzaka 44/52, 01-224 Warszawa, Poland
ABSTRACT
A convenient synthesis of 1ꢀ,2,3,3ꢀ4,4ꢀ-hexa-O-benzylsucrose (4) from the
free disaccharide is presented. Diol 4 and previously obtained 1ꢀ-O-benzy-
loxymethyl-2,3,3ꢀ,4,4ꢀ-penta-O-benzylsucrose (3) served as precursors for
chiral crown ether analogs containing a sucrose backbone. Deprotection of
macrocyclic compounds (removal of the benzyl blocks) was possible under hy-
drogenolysis conditions.
INTRODUCTION
Sucrose with eight free hydroxyl groups can be a very demanding com-
pound to work with and selective protection of these groups presents a signifi-
cant challenge for chemists.1–3 However, chemical differentiation between the
primary and secondary hydroxyl groups is possible and allows preparation of
1ꢀ,6,6ꢀ-tri-O-tritylsucrose in good yield by reaction of sucrose with a large excess
of trityl chloride.4,5 This compound has served as a starting material for the
synthesis of 2,3,4,3ꢀ,4ꢀ-penta-O-benzylsucrose6 (1), in which all secondary hy-
droxyl groups were protected with the blocks easily removable under neutral
conditions. We have also conveniently converted 1 into the corresponding mono
primary alcohols with free 1ꢀ-OH, 6-OH or 6ꢀ-OH groups, respectively, in good
yields.3
*Corresponding author. E-mail: sljar@icho.edu.pl
485
Copyright © 2001 by Marcel Dekker, Inc.
www.dekker.com

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MACH, JAROSZ, AND LISTKOWSKI
Formula 1.
RESULTS AND DISCUSSION
Having a sucrose derivative with the C-6 and C-6ꢀ positions unprotected of-
fers some interesting synthetic opportunities. Connecting those positions via an
oxygen bridge could provide a convenient route to macrocyclic compounds, i.e.,
analogs of crown ethers with an incorporated sucrose backbone. As yet, there are
no examples for the preparation of such sucrose macrocycles, although, chiral
crown ethers containing a carbohydrate unit are known.7
Recently we prepared diol 3 in which the hydroxyl group at the C-1ꢀ posi-
tion was protected as a benzyloxymethyl (BOM) ether (Fig. 1).3 Synthesis of 3
from 1 was rather tedious and required temporary double protection of the most
reactive groups at the C-6 and C-6ꢀ positions by a Mitsunobu reaction with p-ni-
trobenzoic acid leading to 2, followed by conversion of the remaining hydroxyl
function (1ꢀ-OH) into a BOM ether and deprotection at the C-6 and C-6ꢀposi-
tions.3 Synthesis of hexa-O-benzyl sucrose (4) by benzylation of 2 with BnBr-
Ag2O gave the desired product, but in very low yield.
Alternatively, it was reasoned that compound 4 could be prepared by ben-
zylation of 6,6ꢀ-di-O-tritylsucrose (5). However, the latter cannot be obtained in
reasonable yield. Treatment of sucrose with 2 equivalents of triphenylmethyl
chloride gives 6,6ꢀ- (27%), 6,1ꢀ- (4%) and 1ꢀ,6ꢀ- (5%) disubstituted derivatives,8
while tetramolar excess affords 58% of 1ꢀ,6,6ꢀ-tri-O-tritylsucrose and 30% of the
Figure 1. Synthesis of the sucrose diols with free 6,6ꢀ-OH groups.

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487
6,6ꢀ-disubstituted derivative.5 It is clearly seen, therefore, that preparation of 6,6ꢀ-
di-O-trityl sucrose in reasonable yield is not a trivial problem, although reactivity
of the primary hydroxyl groups at the C-6 and 6-6ꢀ-position is much higher than
that of the 1ꢀ-OH group.4,5 The low yield of 5 presumably results from the fact
that the tritylation is not homogeneous, since sucrose has low solubility in pyri-
dine. Therefore, since the concentration of sucrose in solution is rather low, in
contrast to the concentration of the initial tritylation products (either OH group),
the latter are much more reactive than insoluble sucrose.
We reasoned that if all starting material were dissolved in pyridine initially,
the concentration of sucrose would be high enough to take the advantage of the
previously established relative reactivity sequence2 6-OH ꢀ 6ꢀ-OH ꢁ 1ꢀ-OH to
give the 6,6ꢀ-disubstituted derivative 5 as the major product.
Indeed, reaction of an over-saturated homogeneous solution of sucrose in
pyridine with only 2.3 equivalents of triphenylmethyl chloride (3.4 equiv were
used in ref.5) gave the expected C-6,6ꢀ di-protected derivative 5 as a major prod-
uct, together with small amounts of the tri- and mono-tritylated derivatives. Sim-
ple chromatographic separation gave the desired compound 5 in ca. 50% yield.
Standard benzylation (NaH, DMF, BnBr) of the polyol 5 afforded 1ꢀ,2,3,3ꢀ,4,4ꢀ-
hexa-O-benzyl-6,6ꢀ-di-O-tritylsucrose9 (6), deprotection of which with wet
acetic acid furnished the diol 4, without hydrolysis of the glycosidic bond
(Scheme 1). Compound 4 is targeted for eventual use in the preparation of
‘higher sucroses’ (e.g., by functionalization of the di-olefin 7 prepared readily
from 4).
Having access to diol 4, we were able to synthesize several crown ether
analogs containing the sucrose backbone (Scheme 2). Compound 4 and previously
prepared diol 3 were converted into di-anions (by action of sodium hydride in
DMF) which were then reacted with diethylene- and triethylene glycol ditosy-
lates10 under standard conditions7 used for construction of macrocycles, to afford
Scheme 1.

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MACH, JAROSZ, AND LISTKOWSKI
Scheme 2.
the corresponding macrocyclic derivatives 8–11 in yield of 30–50% (Scheme 2).
However, even using the high-dilution technique for cyclization, significant
amounts of the monoprotected derivatives (at either C6 or C6ꢀ positions) were
formed. The macrocycle product was chromatographically separated from the
acyclic products that had been acetylated.
Deprotection of the selected macrocyclic derivative 10 under standard hy-
drogenolysis conditions (H2, Pd/C in aqueous ethanol and ethyl acetate) yielded the
hexaol in quantitative yield, isolated and characterized as peracetate 12.
The macrocycles 8–11 as well as their fully deprotected derivatives will be
used in a study of enantioselective complexation11 of chiral amines and their
derivatives.
CONCLUSION
This report describes a simple and effective preparation of 6,6ꢀ-di-O-tritylsu-
crose (5) in much higher yield than previously reported in the literature. Compound
5 was readily converted into 1ꢀ,2,3,3ꢀ,4,4ꢀ-hexa-O-benzylsucrose (4) by simple
benzylation, followed by removal of the trityl protecting groups. Diol 4 and its ana-
log 3 with free hydroxyl groups at the C-6 and C-6ꢀ positions, were then trans-
formed into several O-benzylated sucrose crown ether analogs. It was possible to

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489
de-O-benzylate the macrocycle 10 by simple hydrogenolysis over palladium on
carbon.
EXPERIMENTAL
1H NMR spectra were recorded with a Varian Gemini 200 or Bruker AM 500
spectrometer for solutions in CDCl3 (internal Me4Si). Most of the proton reso-
nances were assigned by the 1H-1H-correlations and the carbon resonances in 12
by 1H-13C- correlations. Mass spectra (LSIMS; m-nitrobenzyl alcohol was used as
a matrix to which sodium acetate was added or ESI) were recorded with an AMD-
604 or PE SCIEX API 365, or Mariner PerSeptive Biosystems apparatus. Optical
rotations were measured with a Digital Jasco polarimeter DIP-360 for solutions in
chloroform (c 1). Column chromatography was performed on silica gel (Merck,
70–230 or 230–400 mesh). THF and methylene chloride were distilled from potas-
sium or calcium hydride, respectively, prior to use. Dry benzene was stored over
sodium wire. For chromatography purposes a fraction of mineral oil with a boiling
point in range 70–90 °C was used as mixture of hexanes. Acetylation reactions
were performed under standard conditions: acetic anhydride, triethylamine,
DMAP as a catalyst in dry methylene chloride. All solutions were dried over an-
hydrous sodium sulfate.
1ꢀ,2,3,3ꢀ,4,4ꢀ-Hexa-O-benzylsucrose (4). Sucrose (12.0 g; 35 mmol) was
dissolved in pyridine (200 mL) containing DMAP (ca 50 mg) at reflux. After cool-
ing to room temperature, triphenylmethyl chloride (22.0 g; 79 mmol) was added in
one portion (contrary to ref.5 were 3.4 equiv of TrCl were added dropwise) to the
clear solution and the mixture was stirred at rt for 48 h (TLC monitoring in
MeOH–acetone–water–CHCl3, 20:20:3:57). Water (200 mL) was added and the
products were extracted with ethyl acetate (500 mL). The organic phase was
washed with water (2 ꢂ 150 mL), brine (150 mL), dried, concentrated, and the oily
residue was purified by column chromatography (hexane–ethyl acetate, 1:2, then
ethyl acetate–methanol–water, 100:5:2) to afford 6,6ꢀ-di-O-tritylsucrose (5, 15.5 g,
19 mmol, 54%) contaminated with small amounts of other regioisomers. This
crude product was used for the next reaction without further purification. For ana-
lytical purposes, a small amount of this material was acetylated and the desired
1ꢀ,2,3,3ꢀ,4,4ꢀ-hexa-O-acetyl-6,6ꢀ-di-O-tritylsucrose was isolated by column chro-
matography (hexane–ethyl acetate, 3:1 to 1:1): [ꢃ]D ꢄ69.5° (lit.5 [a]D ꢅ ꢄ64.6o);
m/z: 1101 [M(C62H62O17) ꢄ Naꢄ]. NMR (500 MHz) ꢆ7.50 ꢇ 7.00 (m, 30H, Ar-
H), 5.70 (d, 1H, J1,2 ꢅ 3.8 Hz, H-1), 5.35 (t, 1H, J3ꢀ,4ꢀ ꢅ J4ꢀ,5ꢀ ꢅ 4.0 Hz, H-4ꢀ), 5.26
(d, 1H, H-3ꢀ) 5.29 ꢇ 5.17 (m, 2H, H-3 and H-4), 4.82 (dd, 1H, J2,3 ꢅ 10.0 Hz, H-
2), 4.40 and 4.27 (AB system of both H-1ꢀ, JA,B ꢅ 12.6 Hz), 4.21 ꢇ 4.14 (m, 1H,
H-5ꢀ), 4.07 ꢇ 4.01 (m, 1H, H-5), 3.41 and 3.27 (AB system of both H-6ꢀ, J5ꢀ,6ꢀ
ꢅ
6.1 and 6.7 Hz, JA,B ꢅ 9.7 Hz), 3.15 and 2.92 (AB system of both H-6, J5,6 ꢅ 1.7
and 4.1 Hz, JA,B ꢅ 10.5 Hz), 2.09, 2.08, 2.07, 2.00, 1.95, 1.64 (6ꢂs, 6ꢂ3H,
6ꢂOAc). 13C NMR (50 MHz) ꢆ170.1 (double intensity), 169.8, 169.5, 169.3,

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MACH, JAROSZ, AND LISTKOWSKI
168.8 (6ꢂCO), 143.6, 143.4 (2ꢂC), 104.9 (C-2ꢀ), 90.4 (C-1), 86.9, 86.3, 81.0,
70.7, 70.0, 69.6, 68.4 (7ꢂCH), 63.5, 61.9, 61.1 (3ꢂCH2), 20.8, 20.7, 20.6, 20.5,
20.4, 20.3 (6ꢂOAc).
To a stirred solution of the above prepared 5 in DMF (200 mL), was added
sodium hydride (50% dispersion in mineral oil; 8.55 g, 0.17 mol), and the mixture
was stirred for 30 min at rt. Benzyl bromide (16.2 mL, 0.13 mol) was added drop-
wise, and the mixture was stirred at rt for another 2 h. Excess of hydride was de-
composed carefully with water and the mixture was partitioned between water and
ethyl acetate. The organic phase was separated, washed with water, dried, concen-
trated and the product, 1ꢀ,2,3,3ꢀ,4,4ꢀ-hexa-O-benzyl-6,6ꢀ-di-O-tritylsucrose (6,
19.7 g, 76 %) was isolated by column chromatography (hexane–ethyl acetate, 99:1
to 6:1). [ꢃ]D ꢄ20.6°; m/z: 1389 [M(C92H86O11) ꢄ Naꢄ]. 1H NMR (500 MHz) d
6.57 (d, 1 H, J1,2 ꢅ 3.6 Hz, H-1) 13C NMR (125 MHz) d 144.6, 144.2, 140.0, 139.4,
139.3, 139.1, 138.4, 138.1 (quaternary C, 2ꢂTr and 6ꢂBn), 104.9 (C-2ꢀ), 96.4 (C-
1), 89.5 (CH), 87.5 and 86.7 (2ꢂCPh3), 84.8, 82.7, 81.19, 81.17, 79.5, 78.5
(6ꢂCH), 75.8, 75.0, 73.73, 73.68, 73.3, 72.7, 72.3, 71.6, 63.4, 62.7 (10ꢂOCH2).
Anal. Calcd for C92H86O11: C, 80.79; H, 6.34. Found: C, 80.8; H, 6.4.
The above prepared 1ꢀ,2,3,3ꢀ,4,4ꢀ-hexa-O-benzyl-6,6ꢀ-di-O-tritylsucrose (6,
13,0 g; 9,5 mmol) was dissolved in toluene (60 mL) to which water (13.5 mL) and
glacial acetic acid were added (170 mL) and this mixture was boiled under reflux
for 2 h (TLC monitoring in hexane–ethyl acetate, 4:1). Water was added (200 mL),
the mixture was cooled to room temperature, the phases were separated and the
aqueous phase was extracted thrice with ethyl acetate–ether (150 mL : 50 mL). The
combined organic phases were placed in a flask containing water (100 mL). The
pH of the aqueous layer was adjusted to 14 by addition of concd NaOH and the
mixture was stirred for 12 h. The organic phase was separated, washed with water,
brine, dried, concentrated, and 1ꢀ,2,3,3ꢀ,4,4ꢀ-hexa-O-benzylsucrose (4, 4.4 g, 52%)
was isolated by column chromatography (hexane–ethyl acetate, 4:1 to 1:1). It was
possible to remove all impurities at this stage. [ꢃ]D ꢄ40.8°; m/z: 905
[M(C54H58O11) ꢄ Naꢄ].
Anal. Calcd for C54H58O11: C, 73.45; H, 6.62. Found: C, 73.0; H, 6.8.
This compound was characterised as diacetate: [ꢃ]D ꢄ50.6°; m/z: 989
[M(C58H62O13) ꢄ Naꢄ]. 1H NMR (200 MHz) d 5.66 (d, 1 H, J1,2 ꢅ 3.1 Hz, H-1),
1.97 (s, 6H, 2ꢂCH3). 13C NMR (50 MHz) d 170.5, 170.5 (2ꢂCO), 104.6 (C-2ꢀ),
89.7 (C-1), 83.6, 81.8, 81.7, 79.6, 78.2, 77.2 (6ꢂCH), 75.5, 74.8, 73.4, 72.9, 72.6,
72.3, 71.0 (6ꢂOCH2Ph and C-1ꢀ), 69.7 (1ꢂCH), 65.4, 63.6 (2ꢂ CH2OAc), 20.8
and 20.7 (2ꢂOAc).
Methyl [methyl (E)-2,3,4-tri-O-benzyl-6,7-dideoxy-ꢃ-D-gluco-oct-2-en-
1,5-pyranosiduronat-1-yl]-(1(7)-(E)-5,6,8-tri-O-benzyl-2,3-dideoxy-(D-lyxo-
oct-2-en-7-ulo-4,7-furanosidonate (7). To a solution of oxalyl chloride (0.3
mL) in CH2Cl2 (20 mL), DMSO (1.0 mL) was added dropwise at ꢇ78 °C fol-
lowed by a solution of 4 (958 mg, 1.08 mmol) in CH2Cl2 (5 mL). After stirring
for 15 min, triethylamine (2 mL) was added and stirring was prolonged for 1 h.

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The mixture was partitioned between brine (15 mL) and ether (20 mL), the or-
ganic phase was separated, washed with water (10 mL), dried and concentrated.
The residue was dissolved in dry benzene (15 mL) to which was added methoxy-
carbonylmethylene triphenylphosphorane (1.5 g, 4.94 mmol) and the mixture was
stirred at rt for 3 h. Chromatographic purification (hexanes–ethyl acetate, 4:1) af-
1
forded 7 (860 mg, 80%). [ꢃ]D ꢄ65.3°; m/z: 1013 [M(C60H62O13) ꢄ Naꢄ]. H
NMR (500 MHz) ꢆ6.96 (dd, 1H, J5ꢀ,6ꢀ ꢅ 6.1 Hz, J6ꢀ,7ꢀ ꢅ 15.7 Hz, H-6ꢀ), 6.95
(dd, 1H, J5,6 ꢅ 7.8 Hz, J6,7 ꢅ 15.8 Hz, H-6), 6.05 (dd, 1H, J5ꢀ,7ꢀ ꢅ 1.3 Hz, J6ꢀ,7ꢀ
ꢅ 15.7 Hz, H-7ꢀ), 6.01 (dd, 1H, J5,7 ꢅ 1.7 Hz, J6,7 ꢅ 15.8 Hz, H-7), 5.56 (s, 1H,
J
1,2 ꢅ 3.6 Hz, H-1), 4.65ꢇ4.30 (m, 8H, positions of H-5 at d 4.65 and H-5ꢀ at d
4.40 were assigned from H-1H- correlations), 4.071-1141111-114111 (dd, 1H,
J3ꢀ,4ꢀ ꢅ 8.1 Hz, J4ꢀ,5ꢀ ꢅ 8.1 Hz, H-4ꢀ), 4.00 (dd, 1H, J3,4 ꢅ 9.2 Hz, J2,3 ꢅ 9.5 Hz,
H-3), 3.51 (dd, 1H, J1,2 ꢅ 3.6 Hz, J2,3 ꢅ 9.5 Hz, H-2), 3.21 (dd, 1H, J3,4 ꢅ 9.2
Hz, J4,5 ꢅ 9.9 Hz, H-4). 13C NMR (50 MHz,) ꢆ168.6, 168.1 (2ꢂCO), 144.7,
144.4, 122.4, 121.2 (2ꢂCHBCH-CO2Me), 138.5, 138.0, 137.82, 137.77, 137.6
(double intensity; 6ꢂBn), 104.1 (C-2ꢀ), 89.9 (C-1), 84.5, 83.1, 81.8, 81.7, 79.5,
79.1 (6ꢂCH), 75.7, 75.2, 73.4, 73.2, 72.8 (double intensity), 70.9 (6ꢂ CH2Ph
and C-1ꢀ), 69.9 (CH), 51.6, 51.5 (2ꢂCH3).
1
Anal. Calcd for C60H62O13: C, 72.71; H, 6.31. Found: C, 72.5; H, 6.4.
General procedure for the coupling of the O-6 and O-6ꢀ positions in su-
crose diols 3 or 4. Diol 3 or 4 was dissolved in an amount of dry THF to keep
the concentration ca. 10ꢇ2 M/L. Sodium hydride (60 % dispersion in mineral oil,
4 equiv) and catalytic amounts of imidazole (ca. 10 mg) were added and the mix-
ture was stirred at room temperature for 30 min. Then the corresponding ethylene
ditosylate (1.2 equiv) was added and stirring was prolonged at rt for another 6 h.
Excess of sodium hydride was carefully decomposed with water and the products
were extracted with ethyl acetate. The organic phase was washed with water, brine,
dried, and acetylated. Chromatographic isolation of the product afforded the de-
sired macrocycles 8–11.
2,3,3ꢀ,4,4ꢀ-Penta-O-benzyl-1ꢀ-O-benzyloxymethyl-6,6ꢀ-O-di-
ethoxyethylenesucrose (8). Yield 47%. [ꢃ]D ꢄ29.9°; m/z: 1049 [M(C61H70O14)
ꢄ Naꢄ]. 1H NMR (500 MHz) ꢆ5.67 (d, 1H, J1,2 ꢅ 3.6 Hz, H-1). 13C NMR (125
MHz) ꢆ104.0 (C-2ꢀ), 94.8 (OCH2O), 89.5 (C-1), 83.7, 82.1, 82.0 79.9, 79.7, 77.7,
70.8 (7ꢂCH), 75.4, 74.8, 72.6 (triple intensity), 72.0, 71.3, 71.1, 70.9, 70.70,
70.66, 70.57, 69.62, 69.59, 69.50 (5ꢂOCH2Ph, OBOM, 3ꢂOCH2CH2O, C-6, C-
1ꢀ and C-6ꢀ).
Anal. Calcd for C61H70O14: C, 71.33; H, 6.87. Found: C, 71.3; H, 7.0.
1ꢀ,2,3,3ꢀ,4,4ꢀ-Hexa-O-benzyl-6,6ꢀ-O-diethoxyethylenesucrose (10). Yield
1
31%. [ꢃ]D ꢄ46.1°; m/z: 1014 [M(C60H68O13) ꢄ NH4ꢄ]. H NMR (500 MHz) d
5.68 (d, 1H, J1,2 ꢅ 3.6 Hz, H-1). 13C NMR (125 MHz) ꢆ104.3 (C-2ꢀ), 89.6 (C-1),
83.7, 82.1, 82.0, 79.8, 77.7, 77.3 (6ꢂCH), 75.4, 74.8, 73.4, 72.6, 72.5, 72.4, 72.2,

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71.6, 71.2, 71.1, 70.89, 70.86 (12ꢂCH2), 70.81 (1ꢂCH), 70.6, 70.5, 69.5
(3ꢂCH2).
Anal. Calcd for C60H68O13: C, 72.27; H, 6.87. Found: C, 72.2; H, 7.0.
2,3,3ꢀ,4,4ꢀ-Penta-O-benzyl-1ꢀ-O-benzyloxymethyl-6,6ꢀ-O-ethoxyethyle-
nesucrose (9). Yield 51%. [ꢃ]D ꢄ37.3°; m/z: 1005 [M(C59H66O13) ꢄ Naꢄ]. 1H
NMR (500 MHz) ꢆ5.39 (d, 1H, J1,2 ꢅ 3.5 Hz, H-1), 3.51 (dd, 1H, J2,3 ꢅ 9.6 Hz,
H-2), 3.35 (dd, 1H, J3,4 ꢅ 9.0 Hz, J4,5 ꢅ 10.1 Hz, H-4). 13C NMR (125 MHz)
ꢆ103.6 (C-2ꢀ), 94.8 (OCH2O), 90.0 (C-1), 84.1, 83.4, 82.1 80.1, 79.7, 78.9, 70.6
(7ꢂCH), 75.4, 74.7, 73.6, 73.4, 72.9, 72.3, 72.2, 70.9, 70.5, 70.3, 69.9, 69.4, 69.0
(5ꢂOCH2Ph, OBOM, 2ꢂOCH2CH2O, C-6, C-1ꢀ, C-6ꢀ).
Anal. Calcd for C59H66O13: C, 72.08; H, 6.77. Found: C, 71.8; H, 6.8.
1ꢀ,2,3,3ꢀ,4,4ꢀ-Hexa-O-benzyl-6,6ꢀ-O-ethoxyethylenesucrose (11). Yield
40%. [ꢃ]D ꢄ41.2°; m/z: 975 [M(C58H64O12) ꢄ Naꢄ]. 1H NMR (500 MHz) d 5.41
(d, 1H, J1,2 ꢅ 3.4 Hz, H-1). 13C NMR (125 MHz) d 138.8, 138.7, 138.5, 138.4,
138.2, 138.1 (6ꢂ CH2Ph), 103.7 (C-2ꢀ), 89.9 (C-1), 83.9, 83.2, 82.0, 79.89, 79.87,
78.6 (6ꢂCH), 75.4, 74.7, 73.45, 73.40, 73.2, 72.8, 72.4, 72.2, 71.3, 71.0
(10ꢂCH2), 70.6, 70.4, 70.3, 69.8 (4ꢂCH2).
Anal. Calcd for C58H64O12: C, 71.33; H, 6.87. Found: C, 71.3; H, 7.0.
1ꢀ,2,3,3ꢀ,4,4ꢀ-Hexa-O-acetyl-6,6ꢀ-O-diethoxyethylenesucrose (12). 1ꢀ,2,
3,3ꢀ,4,4ꢀ-Hexa-O-benzyl-6,6ꢀ-O-diethoxyethylsucrose (10, 50 mg, 0.05 mmol)
was dissolved in ethanol (10 mL), water (0.25 mL) and ethyl acetate (2 mL). Pal-
ladium on carbon (10%, 10 mg) was added and the mixture was stirred under a hy-
drogen atmosphere for 24 h. Solvents were evaporated under vacuum and traces of
water were removed by co-evaporation with toluene. Pyridine (10 mL) was added
to the residue followed by acetic anhydride (1.5 mL) and DMAP
(5 mg), the mixture was stirred for 15 min at room temperature, concentrated and
the product, hexaacetate 12, was isolated by column chromatography (100% ethyl
acetate) and then further purified by HPLC (100% ethyl acetate). Yield 35 mg
(quant.) mp 148–149 °C. [ꢃ]D ꢄ61.0°; m/z: 731.2315 [M(C30H44O19) ꢄ Naꢄ re-
quires 731.2369]. 1H NMR (500 MHz) ꢆ5.71 (d, 1H, J1,2 ꢅ 3.7 Hz, H-1), 5.44 (dd,
1H, J2,3 ꢅ 10.1 Hz, J3,4 ꢅ 9.9 Hz, H-3), 5.40 (d, 1H, J3ꢀ,4ꢀ ꢅ 5.3 Hz, H-3ꢀ), 5.36
(dd, 1H, J4ꢀ,5ꢀ ꢅ 5.3 Hz, H-4ꢀ), 5,19 (dd, 1H, J3,4 ꢅ 9.9 Hz, J4,5 ꢅ 9.9 Hz, H-4),
4.85 (dd, 1 H, J1,2 ꢅ 3.7 Hz, J2,3 ꢅ 10.1 Hz, H-2), 4,24 ꢇ 4.11 (m, 4H, JA,B ꢅ 12.3,
H-5, H-5ꢀ and AB system of both H-1ꢀ), 3.90 [1H of the AB system of -C(6ꢀ)H2O-
, JA,B ꢅ 11.0 Hz, J5ꢀ,6ꢀ ꢅ 7.6 Hz), 3.80 [1H of the AB system of -C(6)H2O-, JA,B ꢅ
11.1 Hz, J5,6 ꢅ 3.9 Hz], 3.74 ꢇ 3.53 [m, 14H, 6ꢂCH2O, second proton of the AB
system of -C(6ꢀ)H2O- and -C(6)H2O-], 2.19 (s, 3H, CH3CO), 2.10 (s, 3 H,
CH3CO), 2.09 (s, 3 H, CH3CO), 2.07 (s, 3 H, CH3CO), 2.04 (s, 3H, CH3CO), 2.01
(s, 3H, CH3CO). 13C NMR (125 MHz) ꢆ170.1 (double intensity), 169.9, 169.8,
169.6, 169.4 (6ꢂCO), 103.9 (C-2ꢀ), 89.7 (C-1), 81.3 (C-5ꢀ), 76.0 (C-3ꢀ), 75.6 (C-
4ꢀ), 71.6 (C-6ꢀ), 71.4, 71.1, 70.9 (3ꢂCH2O), 70.5 (triple intensity: C-2, 2ꢂCH2O),
70.4 (CH2O), 70.1 (C-3), 69.5 (C-5), 69.3 (C-6), 68.8 (C-4), 62.7 (C-1ꢀ), 20.84,
20.79, 20.74, 20.64, 20.57 (double intensity) (6ꢂOAc).

ORDER
REPRINTS
CROWN ETHER ANALOGS
493
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Received November 27, 2000
Accepted May 2, 2001

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